The Pitfalls of Randomised Controlled Trials (RCTs)
No doubt classical RCTs have their strengths and have long been considered the “gold standard” in evidence-based medicine. However, RCTs present some serious limitations that should be considered:
- The ‘perfect’ RCT is designed strictly with internal validity in mind, as a result external validity is compromised (lack of generalisability)
- Strict inclusion and exclusion criteria to obtain a highly selected patient population
- Conducted under idealised, highly controlled and rigorous conditions
This means that results from RCTs may not always mimic a real life treatment situation and may not be directly applicable to clinical practice implementation!
“In asthma research, RCTs do not take into account key factors that interact with asthma outcomes, such as adherence, rhinitis, and smoking; whereas real life research has shown that these are important.”
Professor David Price
Staying Clinically Relevant: A Growing Demand for Real World Evidence
Real life research offers a powerful way to supplement the results of RCTs by providing a means to:
- Measure whether interventions work in real life as well as they did in RCTs (high external validity)
Unlike RCTs, real life research takes into account real life factors such as comorbidities, concomitant treatments, adherence, patient technique, patient management strategies, access to care, socio-economic status and others
- Provide insight into the long-term effectiveness and safety of new interventions
Unlike RCTs which are run over a short duration
- Observe new side effects or adverse effects not seen previously
- Determine the effectiveness of an intervention versus those already on the market
- Determine whether an intervention is being used properly by prescribing doctors and patients
- Observe results in a wider range of patients due to less specific and more inclusive study criteria
The outcomes are more broadly generalisable than RCTs and the results reflect routine clinical practice more closely than RCTs
Real Life Research Solutions at OPRI
Observational studies can help manufacturers and their stakeholders understand the clinical, patient-centered, and economic burden of disease, as well as real world use, value (e.g. effectiveness, patient-reported outcomes), and safety of interventions in real life.
OPRI can design and conduct high-quality, well-designed observational studies:
- The hypothesis, objectives, patient cohort, analysis plan, and outcomes are defined a priori, resulting in useful hypothesis testing
- Lack of randomisation in observational studies is minimised with statistical techniques, including adjusted analyses and matching processes
- Recall bias is also minimised by the use of prospectively recorded databases instead of clinical observation
- Quality standards for real life research are adhered to. Several checklists have been published to establish these standards (e.g. Respiratory Effectiveness Group’s checklist)
Pragmatic Clinical Trials (PCTs)
Pragmatic clinical trials (PCTs) are randomised trials that compare the effectiveness of two or more interventions in real world settings. They seek to produce clinically applicable real world evidence which answer questions important to manufacturers and their stakeholders.
OPRI can design and conduct PCTs to evaluate the effectiveness of your intervention in real life routine practice conditions.